SAN DIEGO -- In a 3-year Swedish study of patients with mild or
moderate forms of Alzheimer's disease who were taking
cholinesterase inhibitors, varying outcomes were demonstrated in the
different domains of the disease and in the scales used.

The findings show the clinical importance of functional
evaluations, even in the mild stages of Alzheimer's disease (AD),
Carina Wattmo, Ph.D., said at the Clinical Trials Conference on
Alzheimer's Disease.

Some randomized trials, such as that of the anti-beta-amyloid
antibody solanezumab and the medical food souvenaid, "have shown
small but significant positive cognitive effects in mild AD
exclusively," said Dr. Wattmo of the clinical memory research unit
in the department of clinical sciences at Lund University, Maim&
Sweden.

"Placebo-controlled trials longer than 6 months in untreated
AD patients are not allowed for ethical reasons. New, longer studies are
most often performed on patients who are on active treatment with
cholinesterase inhibitors and/or memantine. Therapies expected to modify
disease progression need to be thoroughly evaluated over many years.
Knowledge on the expected longitudinal outcome in different stages of AD
is scarce," she said.

Patients were diagnosed with possible or probable AD; the
population included 734 patients with mild AD and 287 with moderate
disease.

The patients were assessed after 2 months of therapy and every 6
months over the 3-year period, with the Mini-Mental State Examination
(MMSE), the Alzheimer's Disease Assessment Scale-Cognitive subscale
(ADAS-Cog), the Clinician's Interview-Based Impression of Change
(CIBIC), and functional capacity based on the Instrumental Activities of
Daily Living scale (IADL).

The mean age of patients was 75 years, and 64% were female.

At baseline, patients in the mild AD group showed an illness
duration of 2.9 years vs. 3.4 years in the moderate AD group, a
difference that was statistically significant (P = .005). They also had
more years of education (9.6 vs. 9.0 years; P less than .001), and a
better functional capacity based on the IADL score (14.7 points vs. 19.1
points; P less than .001).

Dr. Wattmo reported 3-year results from 306 patients in the mild AD
group and 79 patients in the moderate AD group.

The mean change in MMSE was 3.1 points in the mild AD group vs. 4
points in the moderate AD group, a difference that did not reach
statistical significance (P = .148), she said.

The mean decline in the ADAS-Cog was 6.1 points in the mild AD
group vs. 13.2 points in the moderate AD group, a difference that
reached statistical significance (P less than .001).

In addition, 33% of patients in the mild AD group showed global
CIBIC improvement or no change after 3 years of therapy, compared with
15% in the moderate AD group, a difference that was statistically
significant (P = .002), Dr. Wattmo said.

On the IADL, the mean decline was 6.3 points in the mild AD group
vs. 7.5 points in the moderate AD group, a difference that was not
statistically significant (P = .063).

"Varying outcomes were demonstrated in the different domains
and stages of AD in this study from routine clinical practice," Dr.
Wattmo concluded. "The outcome could be dependent on the scales
used."

dbrunk@frontlinemedcom.com

VITALS

Major finding: After 3 years on cholinesterase inhibitors, patients
with mild Alzheimer's disease had a mean decline of 6.1 points on
the Alzheimer's Disease Assessment Scale-Cognitive subscale, while
those with moderate Alzheimer's had a mean decline of 13.2 points,
a difference that reached statistical significance (P less than .001).